Brain imaging of pain: state of the art

Abstract

Pain is a complex sensory and emotional experience that is heavily influenced by prior experience and expectations of pain. Before the development of noninvasive human brain imaging, our grasp of the brain's role in pain processing was limited to data from postmortem studies, direct recording of brain activity, patient experience and stimulation during neurosurgical procedures, and animal models of pain. Advances made in neuroimaging have bridged the gap between brain activity and the subjective experience of pain and allowed us to better understand the changes in the brain that are associated with both acute and chronic pain. Additionally, cognitive influences on pain such as attention, anticipation, and fear can now be directly observed, allowing for the interpretation of the neural basis of the psychological modulation of pain. The use of functional brain imaging to measure changes in endogenous neurochemistry has increased our understanding of how states of increased resilience and vulnerability to pain are maintained.

Keywords: EEG; PET; arthritis; fMRI; fibromyalgia.

Figure 1

A schematic representation of pain modularity circuitry and the pain matrix. Notes: Nociceptive inputs enter the spinal DH through primary afferent fibers that synapse onto transmission neurons. The projection fibers ascend through the contralateral spinothalamic tract targeting the thalamus, and collateral projections also target mesencephalic nuclei, including the RVM and the midbrain PAG. In the pain matrix, there are two complementary pathways through which pain processing takes place. The medial pathway (dark gray) projects from the medial thalamus to the ACC and IC and processes the affective-motivational component of pain (ie, unpleasantness). The lateral pathway (light gray) projects from the lateral thalamus to the primary and secondary somatosensory cortices (SI and SII) and IC and processes the sensory-discriminative aspect of pain (ie, location and intensity). Increased activation of the PFC is related to decreased pain affect purportedly by inhibiting the functional connectivity between the medial thalamus and the midbrain. Descending projections from the hypothalamus (not shown), amygdala, and rACC feed to the midbrain PAG and to the medulla. Neurons within the RVM project to the spinal or medullary DH to inhibit pain experience. © Springer Science+Business Media, LLC 2012. Reproduced with permission of Springer. Jones AK, Huneke NT, Lloyd DM, Brown CA, Watson A. Role of functional brain imaging in understanding rheumatic pain. Curr Rheumatol Rep. 2012;14(6):557–567. Abbreviations: DH, dorsal horn; RVM, rostral ventral medulla; PAG, periaqueductal gray; ACC, anterior cingulate cortex; IC, insular cortex; PFC, prefrontal cortex; rACC, rostral anterior cingulate cortex.

Figure 2

An example figure produced by a neurochemical PET study. Notes: This diagram was derived from PET imaging of radiotracer ¹¹C-diprenorphine, used to illustrate opioid receptor availability, in patients with OA (n=15) and rheumatoid arthritis (n=2). Regression analysis was performed using the SPM8 software to assess the positive relationship between opioid receptor availability and recent McGill pain scores (as a measure of chronic pain over the past week). This diagram illustrates the positive relationship between chronic pain in these patients and opioid receptor binding in the caudate nucleus, nucleus accumbens, and subcallosal area. The highlighted regions indicate regions of significance. Copyright ©2015 Wolters Kluwer. Reproduced with permission from Brown CA, Matthews J, Fairclough M, et al. Striatal opioid receptor availability is related to acute and chronic pain perception in arthritis: does opioid adaptation increase resilience to chronic pain? Pain. 2015;156(11):2267–2275. Promotional and commercial use of the material in print, digital or mobile device format is prohibited without the permission from the publisher Wolters Kluwer Health. Please contact healthpermissions@wolterskluwer.com for further information. Abbreviations: PET, positron emission tomography; OA, osteoarthritis.

Figure 3

An example figure produced by an EEG study. Notes: (A) Grand average waveforms for each group. (B) Grand average topographic maps for each group. EEG ERP waveforms and topography plots of experimental heat pain elicited onto patients and healthy volunteers. This diagram illustrates how EEG analysis can be used to split cerebral activation of pain into separate temporal components, early/late anticipation and the peak evoked by pain. In addition, the topographic maps illustrate the reduced spatial resolution provided by EEG. Red regions indicate areas of increased activation analysis Copyright © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. Reproduced with Brown CA, El-Deredy W, Jones AK. When the brain expects pain: common neural responses to pain anticipation are related to clinical pain and distress in fibromyalgia and osteoarthritis. Eur J Neurosci. 2014;39(4):663–672. Abbreviations: EEG, electroencephalography; ERP, event-related potential; OA, osteoarthritis; FM, fibromyalgia; ms, millisecond; LEP, laser evoked potential.